TY - JOUR
T1 - Rac1 activation in podocytes induces rapid foot process effacement and proteinuria
AU - Yu, Haiyang
AU - Suleiman, Hani
AU - Kim, Alfred H.J.
AU - Miner, Jeffrey H.
AU - Dani, Adish
AU - Shaw, Andrey S.
AU - Akilesh, Shreeram
PY - 2013/12
Y1 - 2013/12
N2 - The kidney's vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally complex podocyte forms the final cellular barrier to filtration. Injury to the podocyte results in a morphological change called foot process effacement, which is a ubiquitous feature of proteinuric diseases. The exact mechanism underlying foot process effacement is not known, but recently it has been proposed that this change might reflect activation of the Rac1 GTPase. To test this hypothesis, we generated a podocyte-specific, inducible transgenic mouse line that expressed constitutively active Rac1. When the Rac1 transgene was induced, we observed a rapid onset of proteinuria with focal foot process effacement. Using superresolution imaging, we verified that the induced transgene was expressed in damaged podocytes with altered foot process morphology. This work sheds new light on the complex balance of Rho GTPase signaling that is required for proper regulation of the podocyte cytoskeleton.
AB - The kidney's vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally complex podocyte forms the final cellular barrier to filtration. Injury to the podocyte results in a morphological change called foot process effacement, which is a ubiquitous feature of proteinuric diseases. The exact mechanism underlying foot process effacement is not known, but recently it has been proposed that this change might reflect activation of the Rac1 GTPase. To test this hypothesis, we generated a podocyte-specific, inducible transgenic mouse line that expressed constitutively active Rac1. When the Rac1 transgene was induced, we observed a rapid onset of proteinuria with focal foot process effacement. Using superresolution imaging, we verified that the induced transgene was expressed in damaged podocytes with altered foot process morphology. This work sheds new light on the complex balance of Rho GTPase signaling that is required for proper regulation of the podocyte cytoskeleton.
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U2 - 10.1128/MCB.00730-13
DO - 10.1128/MCB.00730-13
M3 - Article
C2 - 24061480
AN - SCOPUS:84891703184
SN - 0270-7306
VL - 33
SP - 4755
EP - 4764
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 23
ER -